
@article{yangCdIIBinding2021,
  ids = {yangCdIIBinding2020},
  title = {Cd({{II}})-Binding Transcriptional Regulator Interacts with Isoniazid and Regulates Drug Susceptibility in Mycobacteria},
  author = {Yang, Min and Jia, Shi-Hua and Tao, Hui-Ling and Zhu, Chen and Jia, Wan-Zhong and Hu, Li-Hua and Gao, Chun-Hui},
  year = {2021},
  month = feb,
  volume = {169},
  pages = {43--53},
  issn = {1756-2651},
  doi = {10.1093/jb/mvaa086},
  abstract = {It is urgent to understand the regulatory mechanism of drug resistance in widespread bacterial pathogens. In Mycobacterium tuberculosis, several transcriptional regulators have been found to play essential roles in regulating its drug resistance. In this study, we found that an ArsR family transcription regulator encoded by Rv2642 (CdiR) responds to isoniazid (INH), a widely used anti-tuberculosis (TB) drug. CdiR negatively regulates self and adjacent genes, including arsC (arsenic-transport integral membrane protein ArsC). CdiR directly interacts with INH and Cd(II). The binding of INH and Cd(II) both reduce its DNA-binding activity. Disrupting cdiR increased the drug susceptibility to INH, whereas overexpressing cdiR decreased the susceptibility. Strikingly, overexpressing arsC increased the drug susceptibility as well as cdiR. Additionally, both changes in cdiR and arsC expression caused sensitivity to other drugs such as rifamycin and ethambutol, where the minimal inhibitory concentrations in the cdiR deletion strain were equal to those of the arsC-overexpressing strain, suggesting that the function of CdiR in regulating drug resistance primarily depends on arsC. Furthermore, we found that Cd(II) enhances bacterial resistance to INH in a CdiR-dependent manner. As a conclusion, CdiR has a critical role in directing the interplay between Cd(II) metal ions and drug susceptibility in mycobacteria.},
  file = {C\:\\Users\\gaoch\\Zotero\\storage\\GG6PK9BH\\Yang et al_2020_Cd(II)-binding transcriptional regulator interacts with isoniazid and regulates.pdf},
  journal = {Journal of Biochemistry},
  keywords = {高春辉一作或通讯论文},
  language = {eng},
  number = {1},
  pmid = {32706888}
}

@article{yangOxiRSpecificallyResponds2019,
  title = {{{OxiR}} Specifically Responds to Isoniazid and Regulates Isoniazid Susceptibility in Mycobacteria},
  author = {Yang, Min and Zhang, Li and Tao, Hui-Ling and Sun, Yuan-Chao and Lou, Zhong-Zi and Jia, Wan-Zhong and Hu, Li-Hua and Gao, Chun-Hui},
  year = {2019},
  month = may,
  volume = {366},
  publisher = {{Oxford Academic}},
  issn = {1574-6968},
  doi = {10.1093/femsle/fnz109},
  abstract = {The bacteria drug resistance is not only associated with the gain of drug resistance gene but also relied on the adaptation of bacterial cells to antibiotics by transcriptional regulation. However, only a few transcription factors that regulate drug resistance have been characterized in mycobacteria. In this study, a TetR family transcriptional factor (OxiR), encoded by Rv0067c in Mycobacterium tuberculosis, was found to be an isoniazid (INH) resistance regulator. Comparing with the wild-type strain, the oxiR overexpressing strain is four times resistant to INH, whereas the oxiR knockout strain is eight times sensitive to INH. However, the rifamycin and ethambutol resistance were not influenced by oxiR. OxiR can bind to self-promoter at a 66 bp imperfect palindromic motifs. Interestingly, OxiR directly binds to INH, and thereby alleviate the self-repression. Furthermore, OxiR negatively regulated an oxidoreductase encoded by Rv0068. And the susceptibility of the Rv0068-overexpressing and oxiR knockout strains to all the three above-mentioned anti-tuberculosis drugs was equivalent, suggesting that the effect of oxiR to INH susceptibility is attributed to the derepression of Rv0068. In conclusion, we showed that OxiR can specifically modulate INH susceptibility by regulating an oxidoreductase encoding gene, both of which have not been associated with drug-resistance previously.},
  file = {C\:\\Users\\gaoch\\Zotero\\storage\\PV38RHJR\\Yang et al_2019_OxiR specifically responds to isoniazid and regulates isoniazid susceptibility.pdf},
  journal = {FEMS microbiology letters},
  keywords = {高春辉一作或通讯论文},
  language = {eng},
  number = {10},
  pmid = {31125044}
}


